ORIGINAL CONTRIBUTION Inclusion complexes of rosmarinic acid and cyclodextrins: stoichiometry, association constants, and antioxidant potential Bruno Medronho & Artur J. M. Valente & Patrícia Costa & Anabela Romano Received: 16 October 2013 /Revised: 11 November 2013 /Accepted: 11 November 2013 /Published online: 5 December 2013 # Springer-Verlag Berlin Heidelberg 2013 Abstract The interaction between β-cyclodextrin (β-CD) and the polyphenol rosmarinic acid (RA) is here reported by 1 H NMR titration experiments. The formation of an aqueous soluble inclusion complex is confirmed and valuable informa- tion regarding mode of penetration of guest into β-CD, stoi- chiometry, and stability of the complex is obtained. The analysis by the continuous variation method shows the un- doubted formation of 1:1 β-CD/RA complex. Additionally, the estimated apparent association constants reveal the impor- tance of the asymmetry of the RA in the complexation; the incorporation of the catechol moiety closer to the carboxylic group is more favorable (K =2,028 M -1 ) than from the other end of the RA molecule (K =1,184 M -1 ). Finally, we have also investigated the antioxidant activity and storage stability of the β-CD/RA complexed system; the presence of β-CD was found to produce a remarkable enhancement on the antioxi- dant activity. Keywords Cyclodextrin . Rosmarinic acid . Antioxidant activity . Continuous variation method . 1 H NMR . Association constant Introduction Cyclodextrins (CDs) are natural macrocyclic oligosaccha- rides, formed by six, seven, or eight glucopyranose units often denoted as α-, β-, or γ-CD, respectively. They have torus- shaped structures with rigid lipophilic cavities [1–3]. The cavity is lined by the hydrogen atoms and the glycosidic oxygen bridges. The nonbonding electron pairs of the glyco- sidic oxygen bridges are directed toward the inside of the cavity, producing a high-electron density and lending it some Lewis base character. As a result of this spatial arrangement of the functional groups in the CDs molecules, the cavity is relatively hydrophobic while the external surfaces are hydro- philic. Because of the relative nonpolar character of the cavity in comparison to the polar exterior, CDs can form inclusion complexes with a wide variety of guest molecules, predomi- nantly due to hydrophobic interactions [4–13]. The guest molecules encapsulated by CDs may change their physical, chemical, and biological properties [14–16]. Therefore, CD host–guest complexes may impart be beneficial modifications of guest molecules such as enhancement of bioavailability, solubility, chemical stability from oxidation, avoid hydrolysis, and photodegradation reactions of labile guest molecules, physical isolation of incompatible compounds, and control of volatility and sublimation [2, 15, 17–19]. These properties, complemented with their nontoxicity toward humans, make these molecules highly suitable for a large range of applications within the colloidal domain, including food technology [20, 21], pharmaceutical and biomedicals [22, 23], and cosmetics [24]. Among the vast role of possible guest molecules, phenolic compounds have deserved spe- cial attention [25–27]. This group of phytochemical com- pounds is one of the major classes of secondary metabo- lites produced by plants with positive health benefits. However, their low bioavailability, due to low absorption and solubility, as well as chemical instability can limit their potential applications and health benefits. For these reasons, an effort has been made regarding the complex- ation of natural polyphenols to maintain their structural integrity and activity [25, 26, 28–33]. In this sense, CDs B. Medronho (*) : P. Costa : A. Romano IBB-CGB, Faculty of Sciences and Technology, University of Algarve, Campus de Gambelas, Ed. 8, Faro 8005-139, Portugal e-mail: bfmedronho@ualg.pt A. J. M. Valente Department of Chemistry, University of Coimbra, Coimbra 3004-535, Portugal Colloid Polym Sci (2014) 292:885–894 DOI 10.1007/s00396-013-3124-5